There are already several known processes and machines for producing granulates, particularly cylindrical granulates. The granulates produced in this way may be used for a variety of different purposes, for example as medicaments with sustained release of the active principle(s), in which case the active principles are embedded by granulation in auxiliaries which in turn contain meltable fats or waxes as binder. In addition, the granulates produced are very often used as intermediate products for the production of plastic articles, for example from thermoplastic plastics.
Thus, Applicants' own DE-AS No. 24 39 538 describes a process for the production of orally administered sustained-release medicaments in which a mixture of powdered active principles, binder and filler is compressed to form cylindrical granulates. This is done by granulating the powder-form mixture of the above-mentioned ingredients, which is plasticizable under heat or pressure, in a gearwheel granulating machine. This gearwheel granulating machine comprises two interengaging holed or perforated plate rollers, i.e. hollow rollers with cylindrical bores or rollers with drilled plates inserted therein. Gearwheel granulating machines such as these compress the powder-form mixture into strands which are then size-reduced to granulates either by means of suitably arranged blades or by grinding. One disadvantage of this process, of which a specific application is described, for example, in the above-mentioned DE-AS No. 24 39 538, lies in particular in the fact that the yield of granulate, based on the quantity of powder-form mixture initially used, is relatively low. This poor granulate yield is attributable above all to the fact that, due to the construction of this gearwheel granulating machine, the sealing of the hollow rollers with the cylindrical bores or of the rollers with the drilled plates inserted therein is very unsatisfactory so that,as a result, up to 50% of the powder-form mixture introduced ends up unchanged as powder or is crushed in the form of so-called blind scabs.
In addition, gearwheel granulating machines of the type in question are attended by design-related disadvantages, including for example an inclination towards increased friction in the vicinity of the granulating rollers which not only involves the danger of local overheating of the powder-form mixture to be granulated, but also results in a relatively high energy demand for operating the gearwheel granulating machine. In addition, it is necessary for design reasons additionally to support the hollow rollers with the cylindrical bores. or the rollers with drilled plates inserted therein in the vicinity of the product.
In addition to the production of granulates by means of gearwheel granulating machines comprising, for example, perforated rollers, there are several other processes and machines by means of which binder-containing, dry or moist powder-form mixtures are forced through sieve openings, perforated plates or nozzles.
Thus, DE-AS No. 10 85 139 for example describes a process for the production of granulate from powder-form material formable under pressure by forcing the powder-form material through a perforated plate by means of a ram or a screw, in which the pressure-forming operation takes place between room temperature and temperatures below the melting point or softening point of the material to be granulated. The press used for carrying out this process comprises a cylinder which is provided at one end with a perforated plate and in which a ram is mounted for displacement, feed lines for the free-flowing powder-form material to be granulated opening into the cylinder in the region of the displacement path of the ram. The openings of the perforations in the perforated plate are preferably wedge-shaped.
In this known process for the production of granulate and the machine used for carrying it out, as in other processes and machines in which binder-containing, dry or moist powder-form materials are forced through sieve openings, perforated plates or nozzles, preliminary compaction of the powder-form material and a length of at least several millimeters for the sieve openings, perforated plates or nozzles are necessary for obtaining the desired, regular and compact granulate particles after the subsequent size-reduction of the pressed material. Hitherto, it has only been special machines of the type used as screw or piston extruders, particularly in the processing of plastics, which have proved suitable for applying the forces required for compaction of the type in question.
In the processing of highly complex mixtures of active principles and auxiliaries of the type described, for example, in the above-mentioned DE-AS No. 24 39 538, the use of machines of the kind in question, which apply the strong forces required, involves numerous development and production problems. One of these problems is that the screw or the piston can easily seize in the screw or piston extruder. In addition, uncontrolled compaction and melting processes can take place ahead of the extrusion nozzle or die. In conjunction therewith and in view of the overall structure of machines of the type in question, the binder-containing, dry or moist powder-form materials can only be processed under intense heat with a loss of active principle(s), mixtures as complex as these of active principle(s) and auxiliaries being in danger of separating in the vicinity of the screw of a screw extruder so that the end product may contain inhomogeneities.
In addition, attempts to overcome the above-mentioned problems by processes and machines in which isostatic compression is applied have only been partly successful.
In processes and machines where isostatic compression is applied, the powder-form material to be compacted is introduced into the depressions of an elastic rubber mould and subjected together with that mould to an isostatic pressure so that the powder-form material is thus compressed. In an isostatic compression process such as this, the mould returns to its original dimensions after removal of the isostatic pressure and the compressed granulate particles lie loosely in the mould depressions and may be removed by upturning the mould. Isostatic compression is used, for example, for the granulation of nuclear fuels.
Compaction into powder-form materials by isostatic compression presupposes that the narrow bores in the die are adequately and uniformly filled before the isostatic compression step. However, only very few powder-form materials have such good flow properties. Above all, such flow properties are non-existent in binder-containing, moist powder-form materials, such as for example mixtures of active principles and auxiliaries of the type described in the above-mentioned DE-AS No. 24 39 538, in which meltable fats or waxes are used as binder. Accordingly, isostatic compression can only be successfully applied in a few special cases.